Nyakeriga, Alice

Abstract [en]

The interaction between nutritional status and malaria disease is complex and often controversial. Nutritional deficiencies (macro- or micro-nutrient) are thought to lead to malnutrition with subsequent susceptibility to malaria infection. On the other hand severe malaria or repeated malaria infections lead to malnutrition. While the cause and effect are difficult to attribute, micronutrient deficiencies such as iron deficiency and malaria infection often co-exist and show complex interactions leading to mutually reinforced detrimental clinical effects.

That iron deficiency has adverse effects on human health is widely recognized. Iron plays a crucial role in processes of growth and cell division and in the transport of oxygen throughout the body. It is also important for the proliferation of cells of the immune system as well as for microorganisms including the malaria parasite. Iron deficiency results in a decrease in hemoglobin concentrations and subsequent anemia. However, the etiology of anemia is multi-factorial and may be affected, in addition, by several factors including malaria and host factors, especially hemoglobinopathies such as alpha-thalassemia and sickle cell trait. These hemoglobinopathies are also common in malaria endemic areas.

In this thesis, we have investigated the relationship between nutritional status, immunity, hemoglobinopathies and falciparum malaria in a cohort of children less than 8 years old living on the coast of Kenya. We have found that malaria was associated with malnutrition in an age-dependent fashion. Malaria was associated with subsequent underweight or stunting in children under the age of 2 years, but this effect was not there in older children. Also, we observed that iron deficiency was associated with protection of children against clinical malaria. Children who were iron deficient had a lower incidence of malaria episodes as compared to those who were iron replete.

While studies on the effects of single micronutrient deficiencies on components of the immune system are difficult to design and interpret, there is ample evidence that micronutrient deficiencies, in general, affect all components of immunity. In line with this, we found that nutritional iron status was associated with certain malaria-specific immunoglobulins and interleukin-4 mRNA levels. Iron deficient children had lower levels of malaria-specific IgG2 and IgG4 but higher expression levels of IL-4 mRNA as compared to the iron replete children. Finally, we observed a tendency towards a higher prevalence of iron deficiency in children carrying either alpha-thalassemia or sickle cell trait.

Grandien, Alf

Troye-Blomberg, Marita

Abstract [en]

Iron deficiency has been reported to affect both malaria pathogenesis and cell-mediated immune responses; however, it is unclear whether the protection afforded by iron deficiency is mediated through direct effects on the parasite, through immune effector functions or through both. We have determined cytokine mRNA expression levels in 59 children living in a malaria endemic area on the coast of Kenya who we selected on the basis of their biochemical iron status. Real-time quantitative reverse transcriptase polymerase chain reaction analysis of cytokine mRNA levels of peripheral blood mononuclear cells (PBMC) obtained from these children showed an association between interleukin-4 (IL-4) mRNA levels and all the biochemical indices of iron that we measured. Furthermore, IL-10 mRNA was higher in parasite blood smear-positive children than in blood smear-negative children irrespective of their iron status. This study suggests that IL-4 expression by PBMC may be affected by iron status.

Wambua, Sammy

Mwacharo, Jedida

Marsh, Kevin

Williams, Thomas

Abstract [en]

Although hemoglobinopathies such as alpha+ thalassemia and the sickle cell trait might contribute to anemia in African children, we hypothesized that they might also enhance iron absorption under circumstances of critical availability, and that this could attenuate their hematologic effects. We found no support for this hypothesis in a cohort of children living on the coast of Kenya.